The objective of the proposed research is to assess the biochemical and clinical effectiveness of various enzyme replacement strategies for the treatment of selected lysosomal storage diseases. Trials of replacement therapy by 1) the administration of unentrapped alpha-galactosidase A isozymes in Fabry's disease and 2) erythrocyte-entrapped beta-glucosidase in Type 1 Gaucher's disease, and 3) the transplantation of arylsulfatase B-producing cells (fibroblasts; hepatocytes) will be evaluated in Maroteaux-Lamy disease. Splenic and plasma alpha-galactosidase A isozymes will be purified by conventional and affinity chromatographic techniques. Purified human placental beta-glucosidase will be entrapped in autologous erythrocytes to maximize protection and to ensure delivery to the site of pathology, the reticulo-endothelial system. The fate, potential physiologic and immunologic consequences, and long-term effects of the administered unentrapped and erythrocyte-entrapped preparations will be assessed in selected patients with Fabry's and Type 1 Gaucher's disease, respectively. The potential of transplanted enzyme producing cells to replace a defective enzymatic activity will be determined. Viable, cultured skin fibroblasts obtained from histocompatable sibling with normal arylsulfatase B activity will be administered intradermally to patients with Maroteaux-Lamy disease. Viable, isolated hepatocytes from normal cats will be administered intraportally to litter-mates with arylsulfatase B deficiency, the feline model of human Maroteaux-Lamy disease. The ability of these hepatocellular grafts to produce normal enzyme will be evaluated prior to human trials of hepatocyte transplantation. The long-term biochemical and clinical effectiveness of these therapeutic strategies in selected patients with these lysosomal storage diseases will be determined.